The previous dogma that the renin–angiotensin system exerts its effects entirely through angiotensin II is now under challenge as scientists explore the properties of the prorenin/renin receptor and start to study local vascular actions of renin independent of its production of angiotensin in the plasma. The demonstrated blood pressure effects of the first clinically developed renin inhibitor, aliskiren, have confirmed the validity of this new class of drugs. Future research, exploring effects on the renin–angiotensin system that perhaps cannot be provided by the currently used blockers of this system, will test whether enhanced clinical benefits might result from this new pharmacologic strategy in patients at risk of cardiovascular events.